This project is designed to examine the following aspects of phosphorothionate insecticide metabolism: 1. What are the relative roles of hepatic and extra-hepatic metabolism of the phosphorothionate insecticides to their toxic phosphate esters as concerns the toxicity of these compounds? 2. What are some of the individual characteristics of the mixed function oxidase enzyme system that metabolizes parathion to paraoxon as compared to that which metabolizes parathion to diethyl phosphorothioic acid? 3. What is the effect of essential fatty acid deficiency and the feeding of a choline-deficient diet on the rate of metabolism of parathion to paraoxon and diethyl phosphorothioic acid? 4. Does the type I binding of parathion to cytochrome P-450 bear any relationship to the formation of a metabolically active enzyme substrate complex? 5. Are there any pathological consequences of the covalent binding of sulfur released in the metabolism of the phosphorothionate insecticides to their corresponding phosphate analogs? 6. What is the chemical form of the sulfur released in the metabolism of the phosphorothionate insecticides to the corresponding phosphates?